U.S. Pat. No. 4,564,628 describes alkyl derivatives of aminotetraline exhibiting dopaminergic activity. Among these compounds, (I) is found,

Subsequent studies, whose results are described in U.S. Pat. No. 4,657,925, show that the dopaminergic action of enantiomer (6S)-(−)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol, hereinafter referred to as S-(I), is up to 140 times higher than that of enantiomer (6R)-(+)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol.
U.S. Pat. No. 4,885,308 describes the use of S-(I), active ingredient known as Rotigotine, for the treatment of Pakinson's disease.
There is, therefore, a need for a process to prepare an optically pure S-(I) enantiomer, which is free of the R-(I) enantiomer.
The processes described so far for the preparation of S-(I) are based on the preparation of intermediate compound (S)-2-(N-propylamino)-5-methoxytetraline, S-(II).
U.S. Pat. No. 4,657,925 discloses the preparation of (S)-2-(N-propylamino)-5-methoxytetraline, S-(II), by resolution of the corresponding racemic mixture. However, no details on the resolution process used are given.
Hoeve et al., J. Org. Chem., 1985, vol. 50, p. 4508-4515, describe the preparation of S-(II) by optical resolution of the racemic mixture by using chiral (R)-(+)-4-(2-chlorophenyl)-5,5-dimethyl-2-hydroxy-1,3,2-dioxaphosphorinano-2-oxide phosphoric acid as an agent for racemic resolution. This methodology is expensive and tedious since it requires the preparation of said agent, which in turn involves an optical resolution step.
Seiler et al., J. Med. Chem., 1986, vol. 29, p. 912-917, describe the preparation of S-(II) by propylation and subsequent debenzylation of (S)-(−)-2-(N-benzylamino)-5-methoxytetraline, a compound whose preparation is described by McDermed et al. J. Med. Chem., 1976, vol. 19, 4, 547-549, by reductive amination of 5-methoxytetralone with benzylamine, crystallization of the diastereoisomeric salt of (−)-mandelic acid enriched in the (S)-enantiomer, optical purification of this salt by means of six successive recrystallizations in ether and finally the release of the amine as a base. The process is time-consuming and costly for its industrial application.
U.S. Pat. No. 4,968,837 describes the resolution of intermediate compound (II) in its enantiomers by using L-(−)-dibenzoyltartaric acid, although—according to the authors' experience of the present invention—a high optical purity cannot be achieved by applying this method, even after successive purifications of the diastereoisomeric salt.
As set out above, none of the preparation methods for S-(II) and, consequently, for S-(I) described so far seems to be satisfactory for its industrial application. There is, therefore, a need to provide an alternative industrial application process for the preparation of rotigotine, S-(I).